ARAI
ARAI
ARAI
Introduction: Tooth agenesis is the most common dental anomaly in humans and is often found in orthodontic
patients. However, severe tooth agenesis (oligodontia) is rare and its characteristics are poorly understood. This
study aimed to investigate tooth agenesis patterns of Japanese orthodontic patients with nonsyndromic oligo-
dontia. Methods: Panoramic radiographs of 228 orthodontic patients (141 females, 87 males) with nonsyn-
dromic oligodontia were selected and permanent tooth agenesis excluding third molars was evaluated.
Influence of cutoff age was tested, tooth agenesis patterns for each quadrant were calculated, and antagonistic
maxillary and mandibular quadrants were merged as the occluding tooth agenesis pattern. Full-mouth tooth
agenesis patterns were also evaluated. Results: The highest prevalence of tooth agenesis was observed in
maxillary and mandibular second premolars, followed by maxillary first premolars. Prevalence of a symmetric
pattern between right and left quadrants was significantly higher than matched patterns between maxillary
and mandibular antagonistic quadrants. Among 456 possible tooth agenesis patterns, 51 and 49 patterns
were observed for the maxillary and mandibular quadrants, respectively, but 215 patterns for the occluding pat-
terns were observed. In addition, 180 full-mouth tooth agenesis patterns were observed in the 228 patients.
Conclusions: Distinct characteristics in highly ranked patterns were observed compared with studies from other
geographic areas, especially in the maxillary arch. Occluding and full-mouth tooth agenesis patterns showed
wide variation, suggesting difficulty in orthodontic diagnosis. (Am J Orthod Dentofacial Orthop 2019;156:238-47)
P
ermanent tooth agenesis is one of the most com- transplantation, radiotherapy, and combination chemo-
mon developmental anomalies in humans1 and is therapy for childhood cancer.11,12 Oligodontia is often
often found in orthodontic patients. It has been associated with genetic syndromes, such as ectodermal
clinically classified into 3 categories—hypodontia, oligo- dysplasia,13 Klinefelter syndrome, incontinentia pig-
dontia, and anodontia—based on the number of menti, and Asperger syndrome.14 Oligodontia may also
undeveloped teeth. Severe hypodontia or oligodontia occur as an isolated nonsyndromic condition, referred
defines agenesis of 6 or more permanent teeth, to as nonsyndromic oligodontia.15
excluding third molars.2-4 The reported prevalence of Severity of nonsyndromic oligodontia is usually
oligodontia has ranged from 0.08% to 0.16% in the related to the number of missing teeth, but the location
general population,5-7 and higher prevalence rates of the missing tooth or agenesis “pattern” can be
were reported for orthodontic patients.8,9 another important aspect in orthodontic diagnosis for
Environmental factors known to interfere with tooth individual cases.16 For example, agenesis of anterior
development include trauma, infection, smoking,10 teeth mainly affects esthetics,17 whereas that of poste-
surgical intervention, hematopoietic stem cell rior teeth influences skeletal growth pattern,18 mastica-
tory function, and orthodontic anchorage. The primary
motivation of orthodontic treatment for nonsyndromic
Department of Orthodontics, Nippon Dental University, School of Life Dentistry
at Tokyo, Tokyo, Japan oligodontia is that of esthetics,18 but functional and
The author has completed and submitted the ICMJE Form for Disclosure of Po- psychologic problems of such young patients are also
tential Conflicts of Interest, and none were reported. serious.19 However, because of the low prevalence of
Address correspondence to: Kazuhito Arai, Professor and Chair, Department of
Orthodontics, Nippon Dental University, School of Life Dentistry at Tokyo, 1- oligodontia, the number of case reports is limited.
9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan; e-mail, drarai@tky.ndu.ac.jp. Accordingly, diagnosis and treatment planning are
Submitted, January 2018; revised and accepted, September 2018. often difficult even for experienced orthodontists. The
0889-5406/$36.00
Ó 2019 by the American Association of Orthodontists. All rights reserved. management of such patients usually requires
https://doi.org/10.1016/j.ajodo.2018.09.015 multidisciplinary treatment that frequently includes
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Arai 239
orthodontics20 to mainly improve coordination of dental oligodontia patients. The purposes of the present study
arches and obtain sufficient space for dental implants,21 were to investigate the characteristics of permanent
which usually requires costly long-term care.22 There- tooth agenesis patterns in orthodontic patients with
fore, epidemiologic studies on the prevalence of tooth nonsyndromic oligodontia in Japan and confirm the
agenesis patterns in nonsyndromic oligodontia are influence of evaluation cutoff age on analyses.
important to estimate health care costs to support
patients and their families.23
Tooth development is a multifactorial phenomenon, MATERIAL AND METHODS
with more than 200 genes expressed during the pro- The study protocol was reviewed and approved by the
cess.24 Among them, relationships between specific Research Ethics Committee of Nippon Dental University,
genetic mutations and tooth agenesis patterns have School of Life Dentistry at Tokyo (NDU-T2013-26).
been suggested for nonsyndromic oligodontia.25,26 The need for informed consent from individual patients
Currently hypothesized genotype-phenotype relation- was waived by the Ethics Committee owing to the
ships included a missense mutation in the MSX1 gene, retrospective and observational design of the epidemio-
which results in agenesis of second premolars, maxillary logic study.
first premolars, and mandibular first molars.1 The PAX9 To estimate the number of hypodontia and oligo-
region also is associated with variable forms of oligo- dontia patients, a preliminary questionnaire survey was
dontia that mainly affect the molars,27,28 and AXIN2 conducted, which included 433 exclusive orthodontic
mutations29 have been shown to affect a wider range clinics of members of the Japanese Association of Ortho-
of tooth types. However, to date, it has been unclear dontists. Completed questionnaires were returned from
precisely how genetic mutations are related to specific 119 clinics (27.5%). According to the survey, 740 pa-
tooth agenesis patterns,30 and interaction between these tients (508 female and 232 male) with hypodontia
candidate genes31 and epigenetic and environmental (excluding oligodontia) and 58 patients (31 female and
factors have also been suggested.30,32 27 male) with oligodontia were found among 11,195
Ethnic differences33 and the influence of genetic new patients (7253 female and 3942 male) in 2012.
background in different geographic areas34,35 on tooth Consequently, we again surveyed all members by mail
agenesis patterns also have been suggested. For to select and send panoramic radiographs of orthodontic
example, studies on hypodontia have shown a higher patients with oligodontia. Initial inclusion criteria were as
prevalence of mandibular incisor agenesis in East follows: patients with agenesis of 6 or more permanent
Asian countries,33,34 although oligodontia is not well teeth, excluding third molars, diagnosed by means of
studied.30 Therefore, to expand current knowledge on an orthodontic clinical examination, with diagnostic re-
hereditary factors of oligodontia, documenting the cords including panoramic radiographic examinations,
characteristics of tooth agenesis patterns in orthodontic cephalometric evaluation, and dental cast analysis.
patients with nonsyndromic oligodontia in different Exclusion criteria were cleft lip or palate, ectodermal
geographic areas may contribute to investigations of dysplasia, or other congenital anomalies.
the influence of genetic background.30,34 Digital images of panoramic radiographs with age,
The minimum cutoff age as an inclusion criterion of sex, dental anomalies, including tooth agenesis
patients may also affect the results of tooth agenesis according to the results of intra- and extraoral clinical
frequency in epidemiologic studies,35 especially in examinations and evaluation of diagnostic records,
patients with mandibular second premolar agenesis and family history on tooth agenesis were sent to the
caused by delayed dental development.36,37 Recent author by mail on CD-ROMs. Before mailing, patients'
meta-analyses38,39 on hypodontia confirmed the personal information (name and address) was removed.
possibility of misdiagnosis of tooth agenesis in A total of 252 panoramic radiographs were collected
patients younger than 13 years. Although patients with from 71 clinics. Because we asked orthodontic clinics to
oligodontia showed a tendency for delayed tooth send information on all former and current patients, we
formation,4 minimum cutoff ages for previous epidemi- could not obtain the total number of patients in the
ologic studies on oligodontia have varied.40 Clinically, a population. Agenesis of permanent teeth, excluding
delay in orthodontic treatment or treatment planning third molars, was independently evaluated by 2 ortho-
until the patient is 13 years of age or older may be too dontists of the Department of Orthodontics, Nippon
late for most patients. Dental University, Tokyo, Japan, using panoramic radio-
I hypothesized that East Asian nonsyndromic graphs displayed on the same 40-inch computer screen.
oligodontia patients exhibit unique tooth agenesis Third molars were excluded from the evaluation because
patterns compared with European nonsyndromic orthodontic treatment rarely includes these teeth.
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240 Arai
During the evaluation process, 1 image was excluded teeth and prevalence (%) of tooth agenesis for each
because of poor image quality. Disagreement between tooth type in maxillary and mandibular arches excluding
the 2 evaluators occurred for 3 patients, whose images third molars were calculated. To evaluate the prevalence
were excluded from the analyses (agreement rate 248/ of tooth agenesis patterns, dental status was evaluated
251 patients, 98.8%). Twenty patients were also and the Tooth Agenesis Code (TAC) value, excluding
excluded based on age for the following reasons: age third molars, was calculated for each quadrant.41
unknown (n 5 2), age younger than 7 years (n 5 17), Numbers of patients with symmetric and asymmetric
and age older than 25 years (n 5 1). Finally, 228 patients patterns and prevalence (%) were calculated for maxil-
(141 female and 87 male, mean age 12.63 6 3.79 years, lary and mandibular arches and then pooled.
range 7 years 2 months to 24 years 3 months) were Numbers of patients with matched and unmatched
selected. Among them, single images were obtained number and prevalence (%) of patterns between antag-
for 217 patients and additional images were obtained onistic maxillary and mandibular quadrants were calcu-
for 11 patients. In these 11 patients, the following lated and then pooled.
numbers of additional images taken during the observa- Symmetric and asymmetric tooth agenesis patterns
tional period or during and after orthodontic treatment between right and left quadrants and matched and un-
were obtained: 2 images (n 5 4), 3 images (n 5 5), 4 im- matched tooth agenesis patterns between maxillary and
ages (n 5 1), and 5 images (n 5 1). For patients with mandibular antagonistic quadrants were compared by
more than 1 image available, the image taken at the old- means of chi-square test at a significance level of 0.05.
est age was used for analysis. The number of missing Numbers of patients with matched and unmatched
teeth was counted for each patient, and medians and in- tooth agenesis patterns in all 4 quadrants and prevalence
terquartile ranges (IQRs) for female and male patients (%) also were calculated.
were calculated and compared by means of the Mann- Tooth agenesis patterns in right and left quadrants
Whitney U test. The number of missing teeth was the were pooled and rankings of the prevalence of tooth
same for both sex groups (median 7.0, IQR 4.0, range agenesis patterns for maxillary and mandibular arches
for females was 6-18, and for males was 6-19 teeth) were created by the pivot table function of Microsoft
and a sex difference was not observed (z 5 0.406; Office Excel 2013 (Microsoft, Redmond, Wash).
P .0.05). Therefore, data in the groups were pooled Tooth agenesis patterns between antagonistic
for subsequent analyses. maxillary and mandibular quadrants were merged as
Tooth agenesis in other family members was reported the occluding tooth agenesis pattern and the prevalence
for 48 patients (21.0%). Four pairs of family members was calculated for right and left sides separately and
were included in this study: sister-sister (n 5 2), then pooled. A ranking of the prevalence of occluding
mother-daughter (n 5 1), and sister-brother (n 5 1). tooth agenesis patterns was also calculated.
No family history was reported for 156 patients Tooth agenesis patterns of the 4 quadrants were
(68.4%), and no answer or family history unknown merged as the full-mouth tooth agenesis pattern of
was reported for 24 patients (10.5%). each patient.16 Then the prevalence and ranking of the
prevalence of full-mouth tooth agenesis patterns were
Analysis calculated.
The number of missing teeth was counted for each The 50% cumulative frequency was calculated for
patient. Patients were then grouped according to age maxillary, mandibular, occluding, and full-mouth tooth
as the younger or older group based on cutoff ages agenesis patterns to evaluate the variation among this
from 8 to 14 years. The mean, standard deviation (SD), cohort. Wider individual variation is indicated when a
median, and IQR were then calculated for younger and larger number of patterns is required to reach 50% total
older age groups. Distributions of the number of missing variation of the sample.13
teeth per patient in each group were evaluated by means
of the Shapiro-Wilk test. No group showed normal dis- RESULTS
tribution; therefore, medians were compared between There was no significant difference in the median
certain age groups older and younger than each cutoff numbers of missing teeth per patient between older
age by means of the nonparametric Mann-Whitney U and younger groups according to cutoff ages set from
test. This statistical comparison was repeated for the 7 8 to 14 years (Table I). A decay curve tendency was
different cutoff ages. observed in the frequency distribution of numbers of
Frequency distribution of the number of missing missing teeth per patient (Fig 1). The greatest number
teeth per patient was counted. The number of missing of missing teeth was observed for maxillary and
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Arai 241
Table I. Comparison of means, SDs, medians, and IQRs of numbers of missing teeth per patient according to different
cutoff ages
$ Cutoff age (older group) \ Cutoff age (younger group)
Fig 1. Frequency distribution of the numbers of missing teeth per patient. A decay curve tendency was
observed.
mandibular second premolars, followed by the maxillary the occluding tooth agenesis pattern, 215 patterns
first premolar (Table II). were observed. The 50% cumulative frequency was
Tooth agenesis patterns in right and left quadrants reached with 27 patterns. Higher-ranked patterns
for the maxillary arch were pooled and 51 patterns included premolars (Fig 4). For the full-mouth tooth
were observed. Tooth agenesis patterns with higher agenesis pattern, 180 patterns were observed for the
prevalence included maxillary first and second premolars 228 patients. Among them, 164 patients showed a
(24.8%), followed by maxillary second premolar only unique pattern. Sixty-six patterns were required to reach
(10.3%). The top 10 ranked patterns included second the 50% cumulative frequency (Fig 5).
premolars. The 50% cumulative frequency was reached Symmetric tooth agenesis patterns between right and
with 5 patterns (Fig 2). Forty-nine patterns were left quadrants were observed in 50% of patients for
observed for the mandibular arch. Agenesis of second both maxillary and mandibular arches, however, only
premolar only (25.0%) and first and second premolars 30% of patients showed a symmetric pattern in both
(20.2%) was prominently higher than other patterns. arches (Table III). Matching tooth agenesis patterns be-
The 50% cumulative frequency was reached with only tween antagonistic maxillary and mandibular quadrants
3 patterns (Fig 3). were observed in 13% of patients. Twelve patients had
When tooth agenesis patterns between antagonistic the same pattern for all 4 quadrants. Affected teeth
maxillary and mandibular quadrants were merged as for 11 patients were first and second premolars, and 1
American Journal of Orthodontics and Dentofacial Orthopedics August 2019 Vol 156 Issue 2
242 Arai
M2
significant difference was found between the prevalence
of tooth agenesis patterns between symmetric right and
left quadrants and matched antagonistic maxillary and
mandibular quadrants (c2 5 179.13; P \0.01).
M1
DISCUSSION
P2
P1
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Arai 243
Fig 2. Ranking of tooth agenesis patterns in the maxillary arch. The top 10 of 51 patterns observed are
shown. Five patterns were required to reach 50% cumulative frequency.
Fig 3. Ranking of tooth agenesis patterns in the mandibular arch. The top 10 of 49 patterns observed
are shown. Three patterns were required to reach 50% cumulative frequency.
populations. However, the remaining 45% of patients control the symmetricity of tooth agenesis should be
showed asymmetric tooth agenesis patterns, conducted.
suggesting the influence of genetic or environmental In the present study, a higher prevalence of tooth
factors. Therefore, further studies on factors that agenesis of individual teeth was found in maxillary
American Journal of Orthodontics and Dentofacial Orthopedics August 2019 Vol 156 Issue 2
244 Arai
Fig 4. Ranking of the occluding tooth agenesis pattern in both maxillary and mandibular arches.
Twenty-seven patterns were required to reach 50% cumulative frequency.
Fig 5. Ranking of the full-mouth tooth agenesis pattern. Sixty-six patterns were required to reach 50%
cumulative frequency.
and mandibular second premolars, followed by maxillary Moreover, tooth agenesis patterns including premo-
first molar, mandibular first premolar, maxillary lateral lars were more frequent in the maxillary arch, and the
incisor, and maxillary and mandibular second molars. highest pattern of maxillary lateral incisor agenesis was
This finding supports Butler's field theory,43 similarly ranked third with only 6% of patients. These findings
to previous European studies.3,6 However, the could be attributed to the higher prevalence of tooth
frequencies of lateral incisor agenesis and mandibular agenesis found in maxillary and mandibular
central incisor agenesis were lower than those second molars (80%) and maxillary first premolar
observed in The Netherlands16 and England,44 respec- (50%). These findings support previous studies on
tively. severe hypodontia patients with 5 or more missing teeth
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